(2S,3R,8aS)-3,8a-dimethyl-2-phenyl-2,3,7,8-tetrahydro-[1,3]oxazolo[3,2-a]pyridine-5-carbonitrile | 191805-46-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: (2S,3R,8aS)-3,8a-dimethyl-2-phenyl-2,3,7,8-tetrahydro-[1,3]oxazolo[3,2-a]pyridine-5-carbonitrile
• CAS: 191805-46-6
• 化学式: C₁₆H₁₈N₂O
• 分子量: 254.332
• InChiKey: UXVXNTJWRQFTGE-WQVCFCJDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  36.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2S,3R,8aS)-3,8a-dimethyl-2-phenyl-2,3,7,8-tetrahydro-[1,3]oxazolo[3,2-a]pyridine-5-carbonitrile 在 2,2,6,6-四甲基哌啶 、 2,2,6,6-tetramethylpiperidinyl-lithium 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 六甲基磷酰三胺 、 正己烷 为溶剂， 反应 3.0h， 生成 (2S,3R,5aS,9aR,10aS)-3,10a-dimethyl-2-phenyl-3,5a,6,9,9a,10-hexahydro-2H-[1,3]oxazolo[3,2-b]isoquinolin-5-one
  参考文献：
  名称：

  Tandem α-Cyano Enamine/Enolate Alkylations on Bicyclic Lactams:  Asymmetric Carbocycle and Heterocycle Synthesis

  摘要：

  The alkylation of cyano enamines 1 and 7 with alpha,omega-dihalides (or dihalide equivalents), followed by hydrolysis to reveal the lactam carbonyl, provided lactams 8 and 10 containing a tethered electrophile. Intramolecular cyclization of the pendant halide onto the lactam enolate provided tricyclic lactams 9 and 13, which were subjected to a second enolate alkylation to form a quaternary stereocenter. In the case of nor-ephedrine tricyclic lactam 13, the intermolecular was highly endo selective, and the resultant lactams 14 were subjected to partial reduction and hydrolytic auxiliary cleavage to provide enantiopure octalones 16 and 17. From this chemistry came the synthesis of the "Woodward ketone" 19, an intermediate in the total synthesis of a number of steroids. Finally, the methoxymethyl bicyclic (or tricyclic) lactams 33 were shown to undergo nonreductive cleavage of the chiral auxiliary to provide 3,4-dihydropyridones containing a quaternary center.

  DOI：

  10.1021/jo971920b
• 作为产物：
  描述：

  左旋去甲麻黄碱 在 copper(l) iodide 、 碘 、 2,4-双(4-苯氧苯基)-1,3-二硫杂-2,4-二磷杂环丁烷-2,4-二硫化物 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 反应 26.0h， 生成 (2S,3R,8aS)-3,8a-dimethyl-2-phenyl-2,3,7,8-tetrahydro-[1,3]oxazolo[3,2-a]pyridine-5-carbonitrile
  参考文献：
  名称：

  手性双环内酰胺作为均烯酸酯的等效物：不对称的路线到5取代的环己烯酮

  摘要：

  双环内酰胺2通过四步高产工艺转化为α-氰胺8。使用THF / HMPA中的LiTMP实现8的γ-金属化，对所得的均烯酸酯等效物进行立体选择性烷基化，然后进行水解，以提供10型内酰胺为单一非对映异构体。内酰胺10的部分还原和水解以良好的总收率提供了对映体纯的5-取代的环己烯酮13。

  DOI：

  10.1016/s0040-4020(97)90391-4

文献信息

• Chiral bicyclic Lactams as homoenolate equivalents: An asymmetric route to 5-substituted cyclohexenones
  作者：Jacob B. Schwarz、Paul N. Devine、A.I. Meyers

  DOI：10.1016/s0040-4020(97)90391-4

  日期：1997.6

  underwent stereoselective alkylation and subsequent hydrolysis to provide lactams of type 10 as a single diastereomer. Partial reduction and hydrolysis of lactams 10 furnished enantiopure 5-substituted cyclohexenones 13 in good overall yield.

  双环内酰胺2通过四步高产工艺转化为α-氰胺8。使用THF / HMPA中的LiTMP实现8的γ-金属化，对所得的均烯酸酯等效物进行立体选择性烷基化，然后进行水解，以提供10型内酰胺为单一非对映异构体。内酰胺10的部分还原和水解以良好的总收率提供了对映体纯的5-取代的环己烯酮13。
• Tandem α-Cyano Enamine/Enolate Alkylations on Bicyclic Lactams:  Asymmetric Carbocycle and Heterocycle Synthesis
  作者：Jacob B. Schwarz、A. I. Meyers

  DOI：10.1021/jo971920b

  日期：1998.3.1

  The alkylation of cyano enamines 1 and 7 with alpha,omega-dihalides (or dihalide equivalents), followed by hydrolysis to reveal the lactam carbonyl, provided lactams 8 and 10 containing a tethered electrophile. Intramolecular cyclization of the pendant halide onto the lactam enolate provided tricyclic lactams 9 and 13, which were subjected to a second enolate alkylation to form a quaternary stereocenter. In the case of nor-ephedrine tricyclic lactam 13, the intermolecular was highly endo selective, and the resultant lactams 14 were subjected to partial reduction and hydrolytic auxiliary cleavage to provide enantiopure octalones 16 and 17. From this chemistry came the synthesis of the "Woodward ketone" 19, an intermediate in the total synthesis of a number of steroids. Finally, the methoxymethyl bicyclic (or tricyclic) lactams 33 were shown to undergo nonreductive cleavage of the chiral auxiliary to provide 3,4-dihydropyridones containing a quaternary center.